Pesticides Linked to Parkinson's

Action Points

Explain to interested patients that this study supports the idea that some pesticides interact with genes in the etiology of Parkinson's disease.

Workplace exposure to some pesticides -- when combined with certain genetic variants -- appears to be linked with an increased risk of Parkinson's disease, researchers said.

In a case-control study, genetic variants in a transporter gene responsible for pumping toxic compounds out of cells were not associated with Parkinson's disease in general, according to Fabien Dutheil, PhD, of Université Paris Descartes in Paris, and colleagues.

But among men, the relationship between organochlorine exposure and Parkinson's disease was approximately 3.5 times stronger in those who carried two variant alleles compared with those who were not carriers, Dutheil and colleagues said in the June issue of Archives of Neurology.

The causes of Parkinson's are likely to be multifactorial, with some environmental factors interacting with genes, the researchers said, and epidemiological studies have shown a consistent link between pesticides and Parkinson's.

"If environmental chemicals can increase Parkinson's disease risk, host factors that contribute to variability in their uptake, metabolism, and distribution in the body may modulate individual risk," the researchers wrote.

One gene that might play a role, they said, is the multidrug resistance protein 1 gene (MDR1 or ABCB1), which encodes P-glycoprotein, a transmembrane transporter that acts as a pump to remove a wide range of molecules from cells.

For this study, the researchers focused on two variants -- dubbed C3435T and G2677(A,T) -- that make P-glycoprotein less effective.

They enrolled 207 people with Parkinson's disease and 482 matched controls, and classified them as never having been exposed to pesticides, exposed through gardening only, or exposed to pesticides through their work.

At the same time, the participants were genotyped for the two genetic variants and -- among the study population as a whole -- the researchers found no significant differences in distribution of the variants between cases and controls.

But when the analysis was restricted to men -- who were judged more likely to have workplace exposure to the chemicals -- the relation between organochlorines and Parkinson's was approximately 3.5 times stronger (with a 95% confidence interval from 0.9 to 14.5) among homozygous carriers of variant G2677(A,T) alleles than among noncarriers.

Again in men, 41% of cases had definite exposure to the compounds, compared with 30% of controls. The difference was significant at P=0.02 and yielded an odds ratio of 2.2 (with a 95% confidence interval from 1.1 to 4.5).

When analysis was restricted to cases, Dutheil and colleagues said, carrying two variant alleles and having been exposed to organochlorines was significantly associated with increased risk. Specifically:

Carrying two alleles of the G2677(A,T) polymorphism yielded an odds ratio of 5.4, with a 95% confidence interval from 1.1 to 27.5, which was significant at P=0.04.

And carrying two alleles of the C3435T polymorphism yielded an odds ratio of 4.1, with a 95% confidence interval from 1.0 to 17.0, which was significant at P=0.05.

One strength of the study, the researchers said, is the use of a detailed pesticide exposure assessment method in a population characterized by a high exposure level.

The main limitation, they said, is the difficulty of accounting for correlated exposures to multiple chemicals. To overcome that, Dutheil and colleagues said, they focused on organochlorines for several reasons, including previous evidence of an association.

They also noted that the interaction analyses were based on small numbers despite the frequency of pesticide exposure in the population.

The findings "support the hypothesis" that genes and pesticides interact in the etiology of Parkinson's, they concluded.

The study had support from INSERM, the Mutualité Sociale Agricole, the Agence Nationale de la Recherche, the Agence Française de Sécurité Sanitaire de l'Environnement et du Travail, the French Ministry of the Environment, France Parkinson, the French Ministry of Education and Research, and Servier Technology.

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